Alteration of reactivity in isolated mesenteric artery from Zucker fatty diabetes mellitus rats

Abstract

Obesity and diabetes are major risk factors for cardiovascular diseases. Zucker fatty diabetes mellitus (ZFDM) rats are novel animal model of obesity and type 2 diabetes. We have recently reported that blood pressure in ZFDM-Lepr^fa/fa (Homo) rats was normal, while blood adrenaline level and heart rate were lower than those in control ZFDM-Lepr^fa/+ (Hetero) rats. Here, we compared the reactivity in isolated mesenteric artery between Hetero and Homo rats. Contraction induced by phenylephrine was increased, while relaxation induced by isoprenaline was decreased in Homo rats at 21-23 weeks old compared with those in Hetero rats. The mRNA expression for α_1A but not β₂ adrenoreceptor in Homo rats was increased. Nitric oxide (NO)-mediated relaxation induced by acetylcholine was decreased, while the mRNA expression for endothelial NO synthase (eNOS) was rather increased in mesenteric artery from Homo rats. These findings for the first time revealed that in Homo rats with reduced plasma adrenaline, blood pressure could be maintained by enhancing vascular contractility induced by adrenaline through the increased α₁ adrenoceptor expression and the attenuated β₂ adrenoceptor signaling. Additionally, NO-mediated endothelium-dependent relaxation is impaired perhaps due to eNOS dysfunction, which might also contribute to maintain the blood pressure in Homo rats.

Keywords: Adrenaline; Arterial contractility; Obesity; Type 2 diabetes; Zucker fatty diabetes mellitus (ZFDM) rats.